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ERβ and Inflammation.

Linnea Hases1,2, Amena Archer1,2, Cecilia Williams3,4

  • 1SciLifeLab, Department of Protein Science, KTH Royal Institute of Technology, Solna, Sweden.

Advances in Experimental Medicine and Biology
|September 15, 2022
PubMed
Summary
This summary is machine-generated.

Estrogen receptor beta (ERβ) plays a protective role in colon inflammation and colitis-associated colorectal cancer by modulating immune signaling and gut microbiota. Selective ERβ activation may offer a preventative strategy.

Keywords:
Circadian clockColonColorectal cancerEstrogen receptorGut microbiotaNFκB

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Area of Science:

  • Endocrinology
  • Immunology
  • Gastroenterology
  • Oncology

Background:

  • Estrogen receptors (ERα and ERβ) modulate inflammatory signals, with ERα's role in breast cancer inflammation well-established.
  • ERβ's function in inflammation is less understood, though its reduced levels are observed in immune organs and colonic cells.
  • Colitis and associated colorectal cancer (CRC) involve complex inflammatory pathways and gut microbiota alterations.

Purpose of the Study:

  • To investigate the role of Estrogen receptor beta (ERβ) in colon inflammation and colitis-associated colorectal cancer (CRC).
  • To explore the mechanisms by which ERβ influences inflammatory signaling pathways, immune cell infiltration, and gut microbiota composition.
  • To assess the potential of selective ERβ activation as a preventative therapeutic strategy for colitis-associated CRC.

Main Methods:

  • Utilized ERβ-selective agonists and ERβ knockout mouse models (full-body and intestinal epithelial-specific).
  • Investigated the interplay between ERβ and key inflammatory pathways, including NFκB and TNFα signaling.
  • Analyzed the impact of ERβ on macrophage infiltration and gut microbiota diversity in models of colon inflammation, including high-fat diet-induced models.

Main Results:

  • ERβ activation was shown to reduce macrophage infiltration during high-fat diet-induced colon inflammation.
  • Evidence supports a crosstalk between ERβ and TNFα/NFκB signaling in the colon.
  • ERβ influences gut microbiota diversity in the context of colitis and colitis-induced CRC.

Conclusions:

  • ERβ is proposed to protect against colitis by modulating NFκB signaling, immune cell infiltration, and gut microbiota composition.
  • Selective activation of ERβ may represent a viable preventative approach for conditions like colitis-associated CRC.
  • Further research into ERβ's anti-inflammatory mechanisms could lead to novel therapeutic strategies for gastrointestinal inflammatory diseases.